Featured Research

from universities, journals, and other organizations

First measurements made of key brain links

Date:

December 4, 2012

Source:

Brown University

Summary:

Until now, brain scientists have been almost completely in the dark about how most of the nonspecific thalamus interacts with the prefrontal cortex, a relationship believed to be key in such fundamental functions as maintaining consciousness and mental arousal. Researchers have performed a set of experiments to explore and measure those circuits for the first time.

Share This

An essential thalamocortical partnership. It’s not just the contact between the thalamus and prefrontal cortex that’s important; it’s the nature of those contacts at different layers of the cortex that allows the thalamus a measure of control. Scott Cruikshank and colleagues used optogenetic techniques to make their findings. Credit: Mike Cohea/Brown University

Until now, brain scientists have been almost completely in the dark about how most of the nonspecific thalamus interacts with the prefrontal cortex, a relationship believed to be key in such fundamental functions as maintaining consciousness and mental arousal. Brown University researchers performed a set of experiments, described in the Journal of Neuroscience, to explore and measure those circuits for the first time.

Related Articles

Inside the brains of mice and men alike, a relatively big football-shaped region called the thalamus acts like a switchboard, providing the prefrontal cortex, the part that does abstract thinking and decision-making, with most of its information. The thalamus's responsibility even includes helping the prefrontal cortex to maintain consciousness and arousal.

Essential as this "thalamocortical" partnership is, neuroscientists have understood very little about the connections coming from a matrix of cells in the so-called "nonspecific thalamus," where information other than from the senses is relayed. In a new paper published Dec. 5, 2012, in the Journal of Neuroscience, Brown University researchers report the first direct measurements in mice of cause-and-effect responses between the key thalamus cells in that matrix and those in the prefrontal cortex.

"These thalamic areas comprise the vast majority of the thalamus, but we know virtually nothing about the physiology of how they control [the] cortex," said one of the lead authors, Scott Cruikshank, assistant professor (research) of neuroscience at Brown.

Among the team's findings is that the nonspecific thalamus signals are most strongly received, at least at first, by inhibitory neurons in the outermost layer of cortex (layer 1). Neuroscientists had assumed that these signals instead mainly poured into excitatory cells of the cortex. It is only over time, with repetition of the thalamic signals, that the inhibitory layer 1 cells respond less strongly while the excitatory cells maintain a steady response. The result is a pattern in which the net effect of the thalamus signals is inhibitory in the cortex at first, but eventually gives way to a steadier, more even state of excitation over a few hundred milliseconds.

A steady state of neuronal excitement could be related to the maintenance of baseline of consciousness or attention.That ultimately sustained pattern of activation stands in stark contrast to the way the sensory signals from the specific thalamus play out in the cortex. The resulting excitation in those circuits starts out strong and then weakens with repetition -- consistent with how people cease to notice sights, smells, and other sensory inputs after a while if they don't change.

A large part of the reason why neuroscientists didn't know this before is because the measurements that Cruikshank and his co-authors made were difficult, if not impossible, to perform using traditional electrical stimulation and recording techniques. Once mouse brain tissue is sliced up, the long connections that the thalamus sends to the cortex, called axons, are severed. Electrically stimulating the axons where they connect to cortex cells, but nothing else around them, was impossible to do.

A relatively new technique called optogenetics made their measurements possible. Optogenetics allows scientists to genetically engineer specific types of neurons so that their activity can be controlled by different colors of light. The team, including co-lead author Omar Ahmed and senior author Barry Connors, chair of neuroscience at Brown, optogenetically engineered the thalamic matrix cells so that their severed axons could be selectively stimulated with light. Because other nearby cell types had not been optogenetically engineered, the light didn't stimulate them, too.

Meanwhile the researchers recorded the electrical activity of the various cortical cells the thalamic axons connected to, to see how they responded to stimulation of the thalamic axons. Sometimes the researchers recorded just the layer 1 inhibitory neurons, sometimes they recorded just the deeper-layered excitatory neurons and sometimes they recorded the different neurons' responses simultaneously. Notably, the outer-layer and deeper-layer cortical neurons are connected to each other as well.

The key results were measurements showing that the inhibitory outer-layer neurons, known as "layer 1 interneurons," have a roughly three-times stronger initial response to the thalamic signals than the deeper excitatory "pyramidal" neurons did. The responses eventually evened out, leading to that steady-state excitement over time.

Cruikshank said the team does not yet know what the behavioral significance of that steady state is, but it could be related to the maintenance of a baseline of consciousness or attention, perhaps to keep the prefrontal cortex ready to accept and process information from other sources, such as sensory signals. Prior experiments have shown that when the nonspecific thalamus is damaged, subjects can fall into a coma, but that when the nonspecific thalamus is stimulated the cortex becomes more aroused.

Now, at least, neuroscientists know how that connection is being made.

In addition to Cruikshank, Ahmed, and Connors, the paper's other authors are Tanya Stevens, Saundra Patrick, Amalia Gonzalez, and Margot Elmaleh. Gonzalez and Elmaleh are former undergraduates whose senior honors theses contributed to the paper.

Funding for the research came from the National Institutes of Health (grants MH086400, NS025983), the Defense Advanced Research Projects Agency (grant BAA-09-27), the National Science Foundation (EFRI-0937848) and the Brown Institute for Brain Science.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 31, 2015  In addition to their physical injuries, women who are victims of domestic violence are also at a greater risk of mental health problems such as depression and psychotic symptoms. "We studied the ... full story

Mar. 31, 2015  New research has scientists re-thinking how a lethal fungus grows and kills immune cells. The study hints at a new approach to therapy for Candida albicans, one of the most common causes of ... full story

Mar. 31, 2015  As the United States faces transplant waiting lists that continue to grow longer over time, there is increasing debate about the proper way to incentivize living donations. Due to organ shortages, ... full story

Mar. 31, 2015  The most virulent strains of Streptococcus suis, the leading cause of bacterial meningitis in adult humans in parts of southeast Asia and in pigs around the world, are likely to have evolved and ... full story

Mar. 31, 2015  A unique pattern of immune molecules in the cerebrospinal fluid of people with myalgic encephalomyelitis/chronic fatigue syndrome have been discovered, providing insights into the basis for cognitive ... full story

Mar. 31, 2015  Children who get a taste of their parents' wine now and then may be more likely than their peers to start drinking by high school, according to a new report. The findings are based on 561 Rhode ... full story

Mar. 31, 2015  Scientists have uncovered the unique mechanism of a powerful natural product with wide-ranging antifungal, antibacterial, anti-malaria and anti-cancer effects. The work sheds light on the natural ... full story

Mar. 30, 2015  Neuroscientists are taking inspiration from natural motor control to design new prosthetic devices that can better replace limb function. Researchers have tested a range of brain-controlled devices ... full story

Mar. 30, 2015  Scientists have found the genetic signature of enterovirus D68 in half of the California and Colorado children diagnosed with acute flaccid myelitis -- sudden, unexplained muscle weakness and ... full story

Mar. 30, 2015  The first study to investigate the relationship between eating fruit and vegetables containing pesticide residues and the quality of men's semen has shown a link with lower sperm counts and ... full story

Featured Videos

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015)  The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports.
Video provided by Reuters

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015)  Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline.
Video provided by Washington Post

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015)  Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17
Video provided by AFP

Related Stories

July 10, 2014  The underlying brain architecture of a person at rest is basically the same as that of a person performing a variety of tasks, a researcher has found. This is important to the study of mental ... full story

Mar. 20, 2013  Cognitive problems with memory and behavior experienced by individuals with schizophrenia are linked with changes in brain activity; however, it is difficult to test whether these changes are the ... full story

Jan. 17, 2013  The pattern of blood flow in the prefrontal cortex in the brains alters with age during multi-tasking, finds a new study. Increased blood volume, measured using oxygenated haemoglobin (Oxy-Hb) ... full story

July 27, 2012  Studies of lucid dreamers show which centers of the brain become active when we become aware of ourselves in dreams. The human capacity of self-perception, self-reflection and consciousness ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.